The aim of this research is to understand the mechanism by which poliovirus infection causes a specific inhibition of host cell protein synthesis while production of viral proteins proceeds efficiently. Infected cell extracts show a loss of the ability to translate capped mRNAs in vitro, although they do function in the translation of viral RNA. This is due to a virus-induced inactivation of a specific translational initiation factor (the cap binding protein complex) which recognizes and binds the 5' cap group on cellular mRNAs, and seems to facilitate the binding of mRNA to the 40S ribosomal subunit. Poliovirus mRNA is not capped and, therefore, presumably can by-pass the requirement for the cap binding protein. Studies proposed in this application will define the biochemical mechanism of the inactivation of cap binding activity, and will result in the purification and identification of the viral mediator of the inactivation reaction. Additional studies are proposed to define the mechanism of ribosome binding and initiation of translation of poliovirus mRNA, which occurs in the absence of a cap group.